title: Regulation of ASIC1 by Ca2+/calmodulin-dependent protein kinase II in human glioblastoma multiforme.
abstract: Recent studies have implicated the acid-sensing ion channel 1 (ASIC1), a proton-gated cation channel that belongs to the epithelial sodium channel (ENaC)/Degenerin family, plays an important role in glioma cell migration. Among the ASIC subunits, only ASIC1a has been found be calcium permeable. However, it has not been determined whether Ca2+/calmodulin-dependent protein kinase II (CaMKII) regulates ASIC1 in glioblastoma multiforme (GBM). Herein, we report that ASIC1 and CaMKII assemble to form a functional complex at the plasma membrane of GBM cells. We found that migration ability was significantly attenuated in GBM cells that were pre-treated with autocamtide-2-related inhibitory peptide (AIP), a CaMKII-specific inhibitor, or psalmotoxin 1 (PcTX-1), a selective ASIC1 blocker. Furthermore, the inhibitory effect of AIP or PcTX-1 on migration was diminished when ASIC1 was knocked down in GBM cells; when ASIC1 knockdown GBM cells were concurrently treated with these two inhibitors, cell migration was slightly but significantly decreased. Using whole-cell patch-clamp recordings, we detected an amiloride-sensitive current in GBM cells, and this current was significantly inhibited by both PcTX-1 and AIP. Moreover, the magnitude of this current was dramatically decreased when ASIC1 was knocked down in GBM cells. The addition of AIP failed to further decrease the amplitude of this current. Taken together, these data suggest that ASIC1 and CaMKII form a functional complex in GBM cells. Furthermore, it can be concluded that CaMKII regulates the activity of ASIC1, which is associated with the ability of GBM cells to migrate.
authors.affiliation: Department of Neurosurgery, the 2nd Affiliated Hospital, Harbin Medical University, Harbin 150086, P.R. China.
authors.forename: Xu
authors.initials: X
authors.lastname: Sun
authors.forename: Dan
authors.initials: D
authors.lastname: Zhao
authors.forename: Yong-Li
authors.initials: YL
authors.lastname: Li
authors.forename: Ying
authors.initials: Y
authors.lastname: Sun
authors.forename: Xu-Hui
authors.initials: XH
authors.lastname: Lei
authors.forename: Jia-Ning
authors.initials: JN
authors.lastname: Zhang
authors.forename: Ming-Ming
authors.initials: MM
authors.lastname: Wu
authors.forename: Rui-Yan
authors.initials: RY
authors.lastname: Li
authors.forename: Zhe-Feng
authors.initials: ZF
authors.lastname: Zhao
authors.forename: Zhi-Ren
authors.initials: ZR
authors.lastname: Zhang
authors.forename: Chuan-Lu
authors.initials: CL
authors.lastname: Jiang
mesh_terms: D062565:Acid Sensing Ion Channels / Q000235:genetics* / Q000378:metabolism; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D002118:Calcium / Q000378:metabolism*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D018408:Patch-Clamp Techniques
chemical_list: C568266:ASIC1 protein, human; D062565:Acid Sensing Ion Channels; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D002118:Calcium